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1 School of Life Sciences and Medical Engineering, Anhui University, Hefei, China.
2 Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China.
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Quan Yuan et al.
Eur J Neurosci.
2026 Sep.
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1 School of Life Sciences and Medical Engineering, Anhui University, Hefei, China.
2 Key Laboratory of Human Microenvironment and Precision Medicine of Anhui Higher Education Institutes, Anhui University, Hefei, China.
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Abstract
This study demonstrates that chronic noise exposure induces anxiety-like behaviors in mice, as consistently observed across three classical behavioral paradigms. Electrophysiological recordings showed that chronic noise exposure is associated with increased intrinsic excitability of serotonergic (5-HT) neurons in the dorsal raphe nucleus (DRN), characterized by a depolarized resting membrane potential, increased spontaneous firing frequency, reduced rheobase, and elevated input resistance. In addition, chronic noise exposure was associated with enhanced excitatory synaptic input onto DRN 5-HTergic neurons, as reflected by an increase in the frequency, but not the amplitude, of both spontaneous and miniature excitatory postsynaptic currents. In contrast, neither intrinsic excitability nor excitatory synaptic transmission of local DRN GABAergic neurons was significantly altered. Furthermore, pharmacological blockade of AMPA and NMDA receptors indicated that the increased excitability of DRN 5-HTergic neurons cannot be fully explained by enhanced excitatory synaptic input alone, suggesting a potential contribution of intrinsic membrane mechanisms. Together, these findings provide correlational evidence that chronic noise exposure is associated with functional alterations in DRN 5-HTergic neurons and may represent a potential neural correlate of noise-related anxiety-like behavior.
Keywords:
anxiety; chronic noise exposure; dorsal raphe nucleus; electrophysiology; serotonin.
© 2026 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Conflict of interest statement
The authors declare no conflicts of interest.
Figures
FIGURE 1
Behavioral performance in the OFT.…
FIGURE 1
Behavioral performance in the OFT. (a) Timeline for noise exposure and behavioral tests…
FIGURE 1
Behavioral performance in the OFT. (a) Timeline for noise exposure and behavioral tests (top) and schematic for noise exposure in a soundproof chamber (bottom). (b) Schematic showing the performance of the control mice and chronic noise exposed mice in OFT. (c) The representative path tracks for moving trajectory in OFT. (d–f) Quantification of the total distance traveled (d), distance traveled in the center zone (e), and time spent in the center zone (f) during the OFT (n = 7 control mice, 6 chronic noise exposed mice). All data are presented as mean ± SEM. n.s., no significant difference; *p < 0.05, **p < 0.01, ***p < 0.001, two‐way ANOVA.
FIGURE 2
Behavioral performance in the EPM…
FIGURE 2
Behavioral performance in the EPM and LDB. (a) Schematic showing the performance of…
FIGURE 2
Behavioral performance in the EPM and LDB. (a) Schematic showing the performance of the control mice and chronic noise exposed mice in EPM. (b) The representative path tracks for moving trajectory in EPM. (c,d) Summarized data for the total travel distance and time in open arms of the EPM (n = 6 control mice, 7 chronic noise exposed mice). (e) Schematic showing the performance of the control mice and chronic noise exposed mice in LDB. (f) The representative path tracks for moving trajectory in LDB. (g) Summarized data for the time in light room of LDB (n = 9 control mice, 10 chronic noise exposed mice). The data are expressed as mean ± SEM. *p < 0.05; **p < 0.01; ***p < 0.001, two‐way ANOVA.
FIGURE 3
Identification of 5‐HTergic and GABAergic…
FIGURE 3
Identification of 5‐HTergic and GABAergic neurons in the DRN of mouse. (a,b) Representative…
FIGURE 3
Identification of 5‐HTergic and GABAergic neurons in the DRN of mouse. (a,b) Representative fluorescence and differential interference contrast (DIC) images of genetically labeled 5‐HTergic and GABAergic neurons. (c) Representative action potentials evoked by depolarizing current injections. (d) Comparison of action potential waveforms between 5‐HTergic and GABAergic neurons. (e) Quantification of evoked firing frequency in 5‐HTergic and GABAergic neurons. Two‐way ANOVA, p < 0.001. (f–i) Quantification of action potential kinetic properties, including peak amplitude (f), half‐width (g), rise slope (h), and decay slope (i). Mann–Whitney U test: (f) p = 0.0096; (g) p < 0.0001; (h) p = 0.7283; (i) p = 0.0019. 5‐HTergic neurons: n = 13 cells from 3 mice; GABAergic neurons: n = 12 cells from 3 mice. The current steps ranged from −40 pA to +80 pA in 10‐pA increments, with each step lasting 600 ms. All data are presented as mean ± SEM. n.s., no significant difference; *p < 0.05, **p < 0.01, ***p < 0.001.
FIGURE 4
Effects of chronic noise exposure…
FIGURE 4
Effects of chronic noise exposure on the neuronal excitability of 5‐HTergic neurons in…
FIGURE 4
Effects of chronic noise exposure on the neuronal excitability of 5‐HTergic neurons in the DRN. (a) Quantification of resting membrane potential (RMP) in control (n = 12 cells from 5 mice, black) and chronic noise exposed (n = 13 cells from 5 mice, red) groups. Mann–Whitney U test, p = 0.0080. (b) Representative traces of spontaneous firing recorded from 5‐HTergic neurons in control and chronic noise exposed mice (left) and quantification of the proportion of spontaneously active neurons in each group (right). (c) Quantification of spontaneous firing frequency in control (n = 9 cells from 3 mice) and chronic noise exposed (n = 9 cells from 3 mice) groups. Mann–Whitney U test, p = 0.0244. (d) Representative traces of action potential firing evoked by somatic current injection in control and chronic noise exposed groups. (e) Quantification of firing frequency as a function of injected current amplitude in control (n = 12 cells from 5 mice) and chronic noise exposed (n = 13 cells from 5 mice) groups. Two‐way ANOVA, p = 0.0032. All data are presented as mean ± SEM. n.s., not significant; *p < 0.05, **p < 0.01, ***p < 0.001.
FIGURE 5
Effects of chronic noise exposure…
FIGURE 5
Effects of chronic noise exposure on membrane properties and action potential kinetics of…
FIGURE 5
Effects of chronic noise exposure on membrane properties and action potential kinetics of DRN 5‐HTergic neurons. (a) Quantification of input resistance (Rin) in control and chronic noise exposed groups. p = 0.0096. (b) Quantification of rheobase in control and chronic noise exposed groups. p = 0.0222. (c) Representative phase‐plane plots of action potentials in control and chronic noise exposed groups. (d–h) Quantification of action potential properties, including voltage threshold (d), peak amplitude (e), half‐width (f), rise slope (g), and decay slope (h). (d) p = 0.3268; (e) p = 0.6114; (f) p = 0.3760; (g) p = 0.1683; (h) p = 0.3760. Control: n = 11 cells from 5 mice; chronic noise exposed: n = 12 cells from 5 mice. All data are presented as the mean ± SEM. n.s., no significant difference; *p < 0.05, **p < 0.01, ***p < 0.001. Mann–Whitney U test.
FIGURE 6
Chronic noise exposure enhances sEPSCs…
FIGURE 6
Chronic noise exposure enhances sEPSCs and mEPSCs of 5‐HTergic neurons in the DRN.…
FIGURE 6
Chronic noise exposure enhances sEPSCs and mEPSCs of 5‐HTergic neurons in the DRN. (a) Representative traces of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from control (black) and chronic noise exposed (red) groups. (b) Cumulative distribution of inter‐event intervals of sEPSCs and quantification of sEPSC frequency (inset) in control and chronic noise exposed groups. p = 0.0016. (c) Cumulative distribution of sEPSC amplitudes and quantification of sEPSC amplitude (inset) in control and chronic noise exposed groups. p = 0.8238. (d) Representative traces of miniature excitatory postsynaptic currents (mEPSCs) recorded from control (black) and chronic noise exposed (red) groups. (e) Cumulative distribution of inter‐event intervals of mEPSCs and quantification of mEPSC frequency (inset) in control and chronic noise exposed groups. p = 0.0079. (f) Cumulative distribution of mEPSC amplitudes and quantification of mEPSC amplitude (inset) in control and chronic noise exposed groups. p = 0.1996. sEPSCs: control (n = 9 cells from 5 mice), chronic noise exposed (n = 11 cells from 5 mice); mEPSCs: control (n = 9 cells from 5 mice), chronic noise exposed (n = 8 cells from 5 mice). All data are presented as mean ± SEM. n.s., no significant difference; *p < 0.05, **p < 0.01, ***p < 0.001. Mann–Whitney U test.
FIGURE 7
Effects of chronic noise exposure…
FIGURE 7
Effects of chronic noise exposure on intrinsic properties of 5‐HTergic neurons. (a) Representative…
FIGURE 7
Effects of chronic noise exposure on intrinsic properties of 5‐HTergic neurons. (a) Representative traces of spontaneous action potential firing in DRN 5‐HT neurons from control and chronic noise exposed mice (left) during glutamatergic synaptic blockade (CNQX + DL‐AP5) and quantification of the proportion of spontaneously active neurons in each group (right). (b) Quantification of spontaneous firing frequency in control and chronic noise exposed groups. Control: n = 11 cells from 5 mice; chronic noise exposed: n = 12 cells from 5 mice. Mann–Whitney U test, p = 0.0022. (c) Representative firing responses of 5‐HT neurons to step current injections of increasing amplitudes in control and chronic noise exposed mice. (d) Quantification of firing frequency as a function of injected current amplitude in control (n = 17 cells from 5 mice) and chronic noise exposed (n = 17 cells from 5 mice) groups. Two‐way ANOVA, p = 0.0020. All data are presented as mean ± SEM. n.s., no significant difference; *p < 0.05, **p < 0.01, ***p < 0.001.
FIGURE 8
Chronic noise exposure does not…
FIGURE 8
Chronic noise exposure does not alter the intrinsic excitability of GABAergic neurons in…
FIGURE 8
Chronic noise exposure does not alter the intrinsic excitability of GABAergic neurons in the DRN. (a) Quantification of resting membrane potential (RMP) in control (gray) and chronic noise exposed (green) groups. p = 0.8820. (b) Quantification of spontaneous firing frequency in control and chronic noise exposed groups. p = 0.2895. (c) Input–output relationship showing firing frequency as a function of injected current amplitude. Two‐way ANOVA, p = 0.9051. (d) Quantification of input resistance (Rin) in control and chronic noise exposed groups. p = 0.6027. (e) Quantification of rheobase in control and chronic noise exposed groups. p = 0.5940. (f) Representative phase‐plane plots of action potentials in control and chronic noise exposed groups. (g–k) Quantification of action potential properties, including voltage threshold (g), peak amplitude (h), half‐width (i), rise slope (j), and decay slope (k). (g) p = 0.8820; (h) p > 0.9999; (i) p = 0.6556; (j) p = 0.9408; (k) p = 0.3702. For (a, c–k): control, n = 9 cells from 5 mice; chronic noise exposed, n = 11 cells from 5 mice. For (b): control, n = 8 cells from 5 mice; chronic noise exposed, n = 7 cells from 4 mice. Statistical significance was assessed using the Mann–Whitney U test, except for (c), which was analyzed using two‐way ANOVA. All data are presented as mean ± SEM. n.s., no significant difference; *p < 0.05, **p < 0.01, ***p < 0.001.
FIGURE 9
Chronic noise exposure does not…
FIGURE 9
Chronic noise exposure does not alter excitatory synaptic transmission onto GABAergic neurons in…
FIGURE 9
Chronic noise exposure does not alter excitatory synaptic transmission onto GABAergic neurons in the DRN. (a) Representative traces of spontaneous excitatory postsynaptic currents (sEPSCs) recorded from control (grey) and chronic noise exposed (green) groups. (b) Cumulative distribution of inter‐event intervals of sEPSCs and quantification of sEPSC frequency (inset) in control and chronic noise exposed groups. p = 0.9626. (c) Cumulative distribution of sEPSC amplitudes and quantification of sEPSC amplitude (inset) in control and chronic noise exposed groups. p = 0.6730. (d) Representative traces of miniature excitatory postsynaptic currents (mEPSCs) recorded from control (gray) and chronic noise exposed (green) groups. (e) Cumulative distribution of inter‐event intervals of mEPSCs and quantification of mEPSC frequency (inset) in control and chronic noise exposed groups. p = 0.6730. (f) Cumulative distribution of mEPSC amplitudes and quantification of mEPSC amplitude (inset) in control and chronic noise exposed groups. p = 0.4234. sEPSCs: control (n = 8 cells from 5 mice), chronic noise exposed (n = 9 cells from 5 mice); mEPSCs: control (n = 9 cells from 5 mice), chronic noise exposed (n = 8 cells from 5 mice). All data are presented as mean ± SEM. Statistical significance was assessed using the Mann–Whitney U test. n.s., not significant; *p < 0.05, **p < 0.01, ***p < 0.001.
All figures (9)
References
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Publication types
Research Support, Non-U.S. Gov’t
MeSH terms
Anxiety* / physiopathology
Dorsal Raphe Nucleus* / physiology
Dorsal Raphe Nucleus* / physiopathology
Excitatory Postsynaptic Potentials / physiology
GABAergic Neurons / physiology
Serotonergic Neurons* / physiology
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